The overall objective of our research is to develop a better understanding of metabolic and membrane transport alteration that might occur in cells of injured lungs. We are studying effect of endotoxin from gram negative bacteria and other agents which are known to damage pulmonary epithelium such as alloxan. The cellular mechanisms in lungs that are being studied are: 1) the enzymatic basis of lactate production, 2) the "energy contents" of cells as measured by ATP, ADP and AMP, 3) the potential cellular mechanism for the mediation of effects of hormones (which might be released in injured lungs) namely the adenylate cyclase and cyclic AMP system, 4) the cellular sodium potassium transport system and associated fluid transport. In order to assess the metabolic roles of specific cell systems of the lung in the pathophysiologic state, we would be studying cellular function in isolated endothelial and type II epithelial cells of the lung. We have measured activities of enzyme lactate dehydrogenase (LDH) and alpha glycerophosphate dehydrogenase (alpha GPDH), as potential mechanisms involved in the lactate production process of lungs, in lung homogenates. Alloxan, which produced a more pronounced lung edema than endotoxin, effected a shift in LDH and alpha GPDH activities to indicate a lesser potential for lactate production in alloxan injury than than in endotoxin exposed lungs. The active sodium-transport was found to be deranged in both alloxan-treated and endotoxic animal lungs. In our future experiments we would study the effect of endotoxin, hypoxia and/or hypoperfusion on the hemodynamic-mechanical and metabolic functions of the isolated-perfused lung. The experiments with isolated cells and those assessing the adenylate cyclase-cAMP system are in progress.